Bis(4,7-dimethyl and 5-dinitro-1,10-phenanthroline) sulfato-oxovanadium(IV)-mediated in vivo male germ cell apoptosis

✍ Scribed by Osmond J. D'Cruz; Fatih M. Uckun

• Book ID: 102292315
• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 355 KB
• Volume: 21
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.764

✦ Synopsis

Oxovanadium(IV) [VO] complexes

of 1,10-phenanthroline are a new class of potent apoptosis-inducing cytotoxic agents against human testicular cancer cells in vitro. The present study investigated the in vivo ability of four(bis)-chelated 1,10-phenanthroline [phen] complexes of sulfato-oxovanadium(IV)-VO(phen) 2 , VO(Cl -phen) 2 , VO(Me 2 -phen) 2 and VO(NO 2 -phen) 2 -with and without substitutions, to induce testicular germ cell apoptosis. Male germ cell loss in mice was measured by determining the epididymal sperm count, testicular weight and histological evaluation of the testes. Repetitive intratesticular injection (7.5 mg kg -1 testis -1 ) of bis-chelated 1,10-phenanthroline complexes of oxovanadium(IV) with 4,7dimethyl [VO(Me 2 -phen) 2 ] and 5-dinitro [VO(NO 2 -phen) 2 ] substitution led to decreased sperm counts and reduced testicular weights. Histopathological examination of testicular sections from VO(Me 2 -phen) 2and VO(NO 2 -phen) 2 -treated mice revealed a marked inhibition of spermatogenesis and preferential loss of maturing, as well as elongated spermatids. In situ evaluation of seminiferous tubule cross-sections by terminal deoxynucleotidyl transferase-mediated FITC-deoxyuridine triphosphate nick end-labeling (TUNEL) and laser scanning confocal microscopy showed characteristic apoptotic germ cells delineating the periphery of the seminiferous tubules. The ability of bis-chelated 4,7-dimethyl-and 5-dinitro-substituted 1,10-phenanthroline complexes of oxovanadium(IV) to induce germ cell apoptosis in vivo may have potential utility in the treatment of human testicular germ cell tumors.